Enzyme Modulators

<p>Potent and irreversible inhibitor of phosphoinositide-3-kinase (PtdIns-3-kinase) with IC50 of 0.1 nM. PX 866 inhibited cell motility and growth of 3D spheroids of glioblastoma, breast, prostate and colon cancer cell lines at low nanomolar concentrations. PX 866 also exhibited anti-tumoral activity in vivo in xenograft models for ovarian and lung cancer.</p>

<p>Amlexanox is an antiallergic and anti-inflammatory drug that has been shown to be effective in treating rhinitis and allergic asthma in clinical studies. It prevents the slow-reacting substance of anaphylaxis (SRS-A) from being released chemically as a mediator and may have antagonistic effects on interleukin-3.</p>

<p>Competitive inhibitor of ceramide-glycosyltransferase used for substrate reduction therapy in lysosomal storage disorders. It inhibits glucosylceramide synthase, which catalyses the initial step in glycosphingolipid biosynthetic pathway. This compound delays the onset of symptoms in type 1 Gaucher disease, Sandhoff disease and Tay-Sachs disease. It also reduces brain abnormalities in mucolipidosis type IV.</p>

<p>Sulbactam is a synthetic antibacterial agent that inhibits bacterial cell wall synthesis. Sulbactam is a potent inhibitor of bacterial DNA-dependent RNA polymerase. The combination of sulbactam and polymyxin B has been shown to have synergistic inhibitory effects on Gram-negative bacteria and is used as an intravenous antibiotic for the treatment of infections caused by Gram-negative bacteria.</p>

<p>Masitinib is an orally bioavailable inhibitor of c-Kit, PDGFR and FGFR3 tyrosine. It is an antineoplastic which has been studied for applications in a range of human diseases including Alzheimers and cancer and is currently used to treat mast cell tumours in animals. As part of a screening study, Masitinib was shown to be highly effective in blocking SARs-CoV-2 replication.</p>

<p>Inhibits histone deacetylase (HDAC)</p>

<p>Inhibitor of BCR-ABL1 kinase</p>

<p>Teniposide is a cytotoxic drug that is used in the treatment of refractory childhood acute lymphoblastic leukemia. It has antitumour activity. It is a type II topoisomerase inhibitor. This drug inhibits DNA synthesis by forming a complex with topoisomerase II and DNA.</p>

<p>Brain-penetrant inhibitor of anaplastic lymphoma kinase (ALK) and proto-oncogene kinase ROS1. It is a reversible ATP-competitor, interacting with P-loop (L1122, G1123, V1130) and K1150 residue of ALK tyrosine kinase. It has major implications in the treatment of non-small cell lung cancer (NSCLC). The compound is used for resensitization of drug resistant, ALK-mutated cancers to crizotinib chemotherapy and was shown to trigger the regression of EML40ALK-driven brain metastases.</p>

<p>Inhibitor of ALK1, ALK2, ALK3 and ALK6 kinases and bone morphogenetic protein (BMP) pathway. LDN 1931189 is a dorsomorphin derivative that inhibits BMP-mediated activation of Smad, Akt and p38 signalling. LDN 193189 promotes differentiation of human pluripotent cells into PAX6+ anterior neural ectoderm. In combination with basic fibroblast growth factor (FGF2), LDN 193189 promotes differentiation of mouse pluripotent stem cells into inner ear sensory epithelium.</p>

<p>Enalapril is a long-acting angiotensin-converting enzyme inhibitor. It is used to treat hypertension and congestive heart failure, as well as chronic cough due to postnasal drip or bronchitis. Enalapril is an active inhibitor of the synthesis of angiotensin II and other vasoconstrictor substances that are involved in the regulation of blood pressure. It binds reversibly to the active site on angiotensin-converting enzyme (ACE) and blocks its activity by forming strong hydrogen bonds with residues on ACE, thereby preventing it from converting angiotensin I into angiotensin II. This leads to a significant reduction in blood pressure.</p>

<p>Inhibits MET, VEGFR1, VEGFR2; VEGFR3 receptor tyrosine kinases; antineoplastic</p>

<p>Dasatinib is a potent inhibitor of tyrosine kinases and is used in the treatment of chronic myelogenous leukemia, gastrointestinal stromal tumors, and other types of cancer. It also inhibits many SRC- family kinases. Dasatinib has been shown to inhibit the proliferation of cancer cells, leading to cell lysis. Additionally, it has anti-angiogenic effects in vivo, inhibiting the development of new blood vessels in solid tumours.</p>

<p>Inhibitor of PDE4 enzyme</p>

<p>Inhibitor of β-lactamase enzymes</p>

<p>Fasudil hydrochloride is a Rho-kinase inhibitor, which is a synthetic compound derived from natural sources, primarily used in scientific research. The mode of action of Fasudil hydrochloride involves the inhibition of Rho-associated protein kinase (ROCK), a crucial player in the regulation of the actin cytoskeleton. By inhibiting ROCK, Fasudil alters various cellular functions, including contraction, motility, proliferation, and apoptosis.</p>

<p>Nicotinamide is a form of vitamin B that is found in food and it used to treat many conditions such as pellagra and acne. It replenishes cellular energy and has anti-inflammatory effects. Nicotinamide is an inhibitor of the enzyme SIRT1 in vitro but can be a stimulator in cells.</p>

<p>4-Methylpyrazole is a competitive inhibitor of alcohol dehydrogenase, which can be used to treat methanol and ethylene glycol poisoning. It is also used to inhibit the metabolism of ethanol by blocking the conversion of ethanol to acetaldehyde. 4-Methylpyrazole is metabolized into 4-methylpyridinium ion (4MP) by alcohol dehydrogenase, which prevents the conversion of acetaldehyde to acetic acid. This results in an increase in blood levels of acetaldehyde and a decrease in blood levels of acetic acid, leading to an accumulation of toxic metabolites such as formic acid. In addition, 4-methylpyrazole inhibits the enzyme glycol dehydrogenase that breaks down glycols into their harmless components. This leads to an accumulation of toxic intermediate products that are converted back into glycols.</p>

<p>Inhibitor of ErbB2 (IC50 = 3 nM) and EGFR kinase (IC50 = 6.4 nM) with anti-proliferative effects. It inhibits ErbB2 receptor autophosphorylation and induces G1 cell cycle block. The CP 724714 treatment induces reduction of downstream ErbB2 receptor tyrosine kinase signalling, tumor cell apoptosis, release of caspase 3 and regression of tumors in in vivo and in vitro models.</p>

<p>Rensocatib is a reversible inhibitor of DPP-1, also known as cathepsin C, which is a peptidase involved in the activation of neutrophil, an elastase-like serine protease in lung tissue. Brensocatib is an oral drug used to treat infections of the airways (lungs) that are characterised by a permanent enlargement and presenting symptoms such as, coughing and greater mucus production (bronchiectasis). Alternative names of brensocatib are INS-1007 and AZD7986.</p>

<p>Ibuprofen is a non-steroidal anti-inflammatory drug (NSAID) used to reduce inflammation, relieve pain and reduce fever. The mechanism of action of ibuprofen has not been fully elucidated, but it may be due to inhibiting the enzyme cyclooxygenase and thus decreasing the synthesis of prostaglandins allowing a reduction of pain and inflammation.</p>

<p>Inhibitor of S-adenosylhomocysteine hydrolase that disrupts histone methylation by EZH2. Anti-proliferative in some breast cancer and invasive prostate cancer cell lines. One of four key molecules required for inducing chemical reprogramming of somatic cells into induced pluripotent stem cells (iPSC).</p>

<p>Inhibitor of fibroblast growth factor receptors (FGFR1, FGFR2 and FGFR3). Demonstrated anti-tumor effects in pre-clinical models of FGFR-driven tumors. AZD 4547 resulted in tumor progression when applied on a patient-derived model of FGFR1-amplified squamous cell lung disease. Antineoplastic effects also observed in FGFR2-amplified gastric cancer.</p>

<p>Moclobemide is a monoamine oxidase inhibitor that is used to treat major depressive disorder and dipolar disorder. This drug’s mechanism of action involves the reversible inhibition of the enzyme MAO-A. The inhibition of this enzyme results in a decreased metabolism and destruction of neurotransmitters thus relieving the symptoms of depression and bipolar disorder.</p>

<p>Orally available prodrug of gemcitabine</p>

<p>Inhibitor of dopamine-?-hydroxylase</p>

<p>COX-2 enzyme inhibitor; anti-inflammatory</p>

<p>Azathioprine belongs to the group of immunosuppressant drugs that suppress the immune system by inhibiting the production of white blood cells (leukocytes). It is used to treat inflammatory diseases, such as rheumatoid arthritis, lupus, and Crohn's disease. Azathioprine is metabolized in the liver. Additionally, this drug inhibits DNA synthesis by binding to nuclear DNA, preventing RNA transcription and protein synthesis in susceptible cells.</p>

<p>Imatinib is a tyrosine kinase inhibitor drug that is used for the treatment of various leukaemias, gastrointestinal stromal tumours and myeloproliferative disease. This drug inhibits the BCR-ABL tyrosine kinase and thus prevents the downstream phosphorylation of target proteins. This drug also inhibits PDGF, SCF and c-kit.</p>

<p>N-ω-Propyl-L-arginine is a selective inhibitor of neuronal nitric oxide synthase (nNOS). This enzyme is involved in the production of nitric oxide, which plays important roles in various physiological and pathological processes in the body. N-ω-Propyl-L-arginine selectively inhibits nNOS, preventing the conversion of L-arginine to nitric oxide. This makes it a useful tool for studying the role of nNOS in various Life Sciences fields, such as neuroscience and cardiovascular research. It can also be used as an enzyme modulator or ligand in drug discovery studies targeting nNOS.<br>N-ω-Propyl-L-arginine is part of our Bio-X ™ Range. These products are aimed at life science researchers who need high quality ready-to-use products for assay development, screening or other R&amp;D work. With a solubility datasheet and convenient vials, all of our Bio-X ™ products are in stock across our global warehouses for rapid delivery and ease of use.</p>

<p>Inhibitor of HIF-prolyl hydroxylase isozymes PHD1, PHD2 and PHD3 with Ki in nanomolar range. The compound mimics the binding of N-oxalylglycine, chelates catalytic iron and prevents substrate entry into catalytic site. Inhibition of PHD enzymes leads to stabilization of hypoxia-induced factors HIF1α and HIF2α, followed by the production of erythropoietin (EPO).</p>

<p>TAS 6417 hydrochloride is a small-molecule inhibitor, which is synthesized via chemical processes in pharmaceutical research. It functions primarily as a potent and selective inhibitor of specific mutant forms of the epidermal growth factor receptor (EGFR). By targeting these EGFR mutations, TAS 6417 hydrochloride disrupts the signaling pathways that are crucial for the proliferation and survival of cancer cells.</p>

<p>PI3K enzyme inhibitor; antineoplastic</p>

<p>Inhibitor of CDK4/6 serine/threonine kinases; antineoplastic</p>

<p>Inhibitor of prolyl 4-hydroxylase PHD</p>

<p>A potent and selective covalent inhibitor of fibroblast growth factor receptor 4 (FGFR4). This receptor tyrosine kinase activates an oncogenic driver in hepatocellular carcinoma, the fibroblast growth factor 19 (FGF19). The FGFR4 inhibitor is therefore a promising candidate for the treatment of advanced liver cancer.</p>

<p>Inhibitor of metalloendopeptidase neprilysin</p>

<p>Tipifarnib is a farnesyltransferase inhibitor, which is a synthetic compound designed for experimental cancer treatment. It functions by targeting farnesyltransferase, an enzyme involved in the post-translational modification of proteins through the attachment of a farnesyl group to the protein's cysteine residue. This modification is crucial for the activity of several proteins, including those in the Ras signaling pathway, which is often dysregulated in cancer.</p>

<p>Inhibits c-MET tyrosine kinases</p>

<p>A selective inhibitor of PI3Kα. Inhibits cancer cell proliferation by blocking the G0/G1 phase of the cell cycle. Anti-tumor effect of BYL 719 has been demonstrated in models of tumors with PI3KCA mutation and amplification in vivo. BYL 719 also suppresses tumor growth in pre-clinical models of osteosarcoma.</p>

<p>Dual IGF-1R and InsR kinase inhibitor; antineoplastic</p>

<p>Letrozole is an aromatase inhibitor drug that is used in the treatment of breast cancer in postmenopausal women. It is a non-steroidal type II inhibitor that blocks the active site and thus blocking the electron transfer chain of CYP19A1. As a result of this, the conversion of androgen to estrogen is inhibited.</p>

<p>A potent non ATP-competitive inhibitor of MAP/ERK kinase (MEK). Has anti-tumor activity in melanoma and papillary thyroid cancer cells with B-Raf mutations. Enhances generation and survival of induced pluripotent stem cells (iPSCs).</p>

<p>Tacrolimus is a calcineurin inhibitor drug that is used for the prevention of rejection after an organ transplant. This drug can also be used in the treatment of severe atopic dermatitis. Tacrolimus’ mechanism of action is not well known however it is understood that this drug inhibits T-lymphocyte activation by binding to an intracellular protein called FKBP-12. This drug also has anti-inflammatory properties.</p>

<p>Caspase Modulator I, 1541 is a chemical compound designed to modulate the activity of caspases, a family of cysteine proteases critical in the regulation of apoptosis and inflammation. This product is synthesized through advanced chemical processes to ensure high specificity and potency. Its mode of action involves the selective inhibition and modulation of caspase activity, thereby influencing apoptotic pathways and immune responses.</p>

<p>Potent inhibitor of dual specificity tyrosine-phosphorylation-regulated kinase 3 (DYRK3) with IC50 value of 0.7 nM. Elevates hemoglobin and platelet levels in anemic mice.</p>

<p>Lisinopril is a drug that belongs to the group of angiotensin converting enzyme (ACE) inhibitors. It is used to treat hypertension, heart failure and myocardial infarction. Lisinopril binds to the active site of the ACE enzyme, preventing it from converting angiotensin I into angiotensin II.</p>

<p>JAK3 enzyme inhibitor</p>

<p>Nonsteroidal anti-inflammatory (NSAID)</p>

<p>Inhibitor and pseudosubstrate of DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT). It is used as a sensitizer for the treatment of advanced solid tumors, including prostate, colorectal and central nervous system malignancies. Lomeguatrib inhibits the repair mechanism of DNA damage induced by alkylating agents such as temozolomide, and therefore potentiates its anti-cancer effects.</p>